1. Field of the Invention
The present invention relates in general to an optofluidic architecture for label free, highly parallel, detection of molecular interactions. The approach is based on the use of arrays of optically resonant devices, each of which has a resonant wavelength that is shifted due to a local change in refractive index caused by a positive binding event between a surface bound molecule and its solution phase target.
2. Description of the Background Art
Recent interest in the development of new nucleic acid biosensors and high-throughput screening techniques has been largely driven by the potential for associating individual or multiple point polymorphisms with disease states or pharmacological responses, and the need to rapidly diagnose emerging viral threats. To capitalize on these applications, successful next generation sensor platforms should: (1) maximize the total number of biomarker targets against which a sample or multiple samples can be interrogated; (2) minimize the total amount of time and handling required to perform a complete assay; (3) be sufficiently sensitive and specific so as to enable very low, sub-femtogram level detection without the need for target labeling; and (4) minimize the total cost per test.
Existing sensor systems can be separated into traditional and emerging technologies. High-throughput nucleic acid microarrays represent the existing technology which, at present, comes closest to meeting all of the above conditions (addressing (1) and (4) very well and conceivably (2) after incorporation with a suitable microfluidics element, however tending to fail on (3)). To address this failing, emerging nanotechnologies such as nanoparticles, nanowires, nanotubes and nanomechanical or nanophotonic resonators have been developed and represent a quantum leap in terms of sensitivity. The strength of emerging nanosensor technologies is not necessarily that the overall sensitivity is much greater but that the surface area which is probed is much smaller. For example, nanowire devices have achieved very low level detection limits not by increasing the overall sensitivity of the device but by decreasing the binding surface area that is probed. The same is true for nanoparticle based surface plasmon resonance (SPR) and other nanophotonic resonators, and is analogous for nanomechanical resonators. In principal then the challenge in detecting rare solution phase targets is to develop sensors which minimize the resolvable signal multiplied by the probed surface area. In general, nanoparticle based SPR tends to have the smallest probed volume, but tends to have relatively broad adsorption or scattering spectra.
Of the array of optically resonant structures which have been developed into biosensors, planar silicon waveguide resonators and photonic crystals have the next smallest probed surface area. Traditional nanophotonic waveguide resonators are well known to be extremely sensitive to small changes in refractive index and thus have proven themselves to be useful as biological and chemical sensors. Photonic crystal resonator cavities possess very high Q-factors and are very sensitive to changes in the refractive index of their structural elements. They consist of a 1-D or 2-D photonic crystal with a defect in the crystal structure which acts as the resonant cavity. One type of known 2-D photonic crystal microcavity consists of a periodic lattice of cylindrical wells or holes on the order of 100 nm in radius and 200 nm deep in a silicon layer with a central hole defect. Changes in the refractive index in these holes shift the resonant peak which allows them to measure the refractive index of the surrounding liquid medium. In another type of device, a silicon waveguide is flanked on either side by a 1-D or 2-D photonic crystal which causes light corresponding to the photonic bandgap to remain guided in the waveguide. Adsorption of proteins or other biomolecules on the surface of the photonic crystal shifts the bandgap which is detected by observing the transmission spectrum of the waveguide.
While being a novel technique for performing label-free sensing, the extension of these technologies to the extreme parallelity and specificity of the microarray format is complicated by the challenges involved in functionalization of individual sensor elements and two dimensional optical or electrical addressing of reaction sites with sub-micrometer spacing. More specifically, inherent in the nature of such devices is the existence of a band gap surrounding the resonant peak which prohibits optical transmission over a large range of wavelengths (typically on the order of 100 nm). This generally negates the possibility of multiplexing different reaction sites along a single optical structure, thereby prohibiting two dimensional multiplexing.